Correspondence
These conflicting findings are further Probiotics and
reinforcement that greater case
Published Online numbers are urgently required to
April 24, 2020
https://doi.org/10.1016/
accurately inform our understanding
S2468-1253(20)30122-9
of individual risk.
Collating and analysing rapidly
emerging data will be vital for
identifying modifiable risk factors
for severe COVID-19 among liver
transplant recipients. For example,
different immunosuppression
regimens might confer differential
risk and changes to these medications
might mitigate the risk of COVID-19
complications.
See Online for appendix Although early data suggest that
the effects of COVID-19 on the
liver might be modest and reflect
infection severity among patients
without pre-existing liver disease,
the effects of COVID-19 on those
with liver transplants or established
liver disease remain unclear.2 We call
on all those caring for patients with
previous liver transplantation and
other forms of chronic liver disease
to use registries to pool details
of COVID-19 cases and so permit
the rapid large-scale collaborative
analyses that are required to inform
clinical care.
We declare no competing interests.
We acknowledge the work of all the other members
of COVID-Hep and SECURE Cirrhosis, and those who
have already submitted data (appendix). This work
See Online for appendix
was supported by the US National Institutes of
Health (T32 DK007634).
*Gwilym J Webb, Andrew M Moon,
Eleanor Barnes, A Sidney Barritt,
Thomas Marjot
gjwebb@protonmail.com
Translational Gastroenterology Unit, John Radcliffe
Hospital, Oxford University Hospitals, Oxford
OX3 9DU, UK (GJW, EB, TM); and Division of
Gastroenterology and Hepatology, University of
North Carolina School of Medicine, Chapel Hill, NC,
USA (AMM, ASB)
1 Bhoori S, Rossi RE, Citterio D, Mazzaferro V.
COVID-19 in long-term liver transplant
patients: preliminary experience from an
Italian transplant centre in Lombardy.
Lancet Gastroenterol Hepatol 2020; published
online April 9. https://doi.org/10.1016/
S2468-1253(20)30116-3.
2 Zhang C, Shi L, Wang F-S. Liver injury in
COVID-19: management and challenges.
Lancet Gastroenterol Hepatol 2020;
5: 428–30.
644 www.thelancet.com/gastrohep Vol 5 July 2020
pneumonia compared with placebo.9,10
COVID-19: one size does
not fit all
As of April 20, 2020, coronavirus
disease 2019 (COVID-19) has affected
more than 2 million people globally.
In February, 2020, China’s National
Health Commission and National
Administration of Traditional Chinese
Medicine suggested the use of
probiotics in patients with severe
COVID-19.1 We reviewed the evidence
for the role of probiotics in COVID-19-
related illnesses (appendix).
In China, 58–71% of patients with
COVID-19 were given antibiotics,
and diarrhoea occurred in 2–36%
of patients.2–4 When antibiotics are
used, reinforcement of colonic flora
using probiotics has been proposed
to reduce susceptibility to subsequent
infections. Although a 2012 meta-
analysis5 showed that probiotics have
modest efficacy in reducing antibiotic-
associated diarrhoea, the largest
randomised, placebo-controlled trial
(involving 2941 participants) showed
that a 21-day treatment of combined
Lactobacilli and Bifidobacteria did not
reduce antibiotic-associated diarrhoea.6
Even if probiotics are useful, they
are unlikely to have a direct effect on
severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) infection;
most patients with COVID-19 present
with respiratory symptoms. However,
gut–lung crosstalk has been proposed
in the pathogenesis of certain
respiratory conditions. Two meta-
analyses reported modest efficacy of
probiotics in reducing the incidence
and duration of respiratory tract
infections of viral origin.7,8 During the
COVID-19 pandemic, 2–47% of infected
patients required invasive mechanical
ventilation. 3,4 Two randomised
controlled trials showed that critically ill
patients on mechanical ventilation who
were given probiotics (Lactobacillus
rhamnosus GG, live Bacillus subtilis,
and Enterococcus faecalis) developed
substantially less ventilator-associated
However, the efficacy of probiotics
in reduction of intensive care unit
mortality and inpatient mortality is
uncertain.
Scarce data are available on the
effect of COVID-19 on intestinal
microbiota. A small case series from
China revealed that some patients
with COVID-19 showed microbial
dysbiosis with decreased Lactobacillus
and Bifidobacterium.11 However, animal
studies (as yet, not peer-reviewed)
showed that Lactobacillus acidophilus
and Bacillus clausii did not reduce
coronavirus receptor expression in
the murine small intestine compared
with control and post-Salmonella
infection models.12 Not all probiotics
are likely to be the same. Lactobacilli
and Bifidobacteria are only two types
of non-pathogenic bacteria and we
must consider whether they can
really tip the balance of a diverse gut
ecosystem in combating COVID-19. To
date, the rationale for using probiotics
in COVID-19 is derived from indirect
evidence. Blind use of conventional
probiotics for COVID-19 is not
recommended until we have further
understanding of the pathogenesis
of SARS-CoV-2 and its effect on gut
microbiota. It is likely that a novel and
more targeted approach to modulation
of gut microbiota as one of the
therapeutic approaches of COVID-19
and its comorbidities will be necessary.
JWYM reports grants from Janssen, the Hong Kong
College of Physicians, and the Hong Kong Society of
Gastroenterology, outside the submitted work.
FKLC reports grants from Olympus Hong Kong and
China, Pfizer, AstraZeneca, Takeda Pharmaceuticals,
Takeda (China) Holdings, and Given Imaging; and
personal fees from the American
Gastroenterological Association, Medical
Association of Guangdong Province, Olympus Hong
Kong and China, Pfizer, AstraZeneca, Takeda
Pharmaceuticals, EA Pharma, Takeda (China)
Holdings, Associação dos Médicos Hospitalares da
Função Pública de Macau, Pfizer Upjohn Korea,
Fujifilm, Ministry of Health Singapore, and Japanese
Gastroenterological Endoscopy Society. He is also an
advisor and commentator for evidence-based
medicine for the Ministry of Health of the People’s
Republic of China, Pfizer, AstraZeneca, Ministry of
Health Singapore, American College of Physicians
Journal Club, and Nature Reviews Gastroenterology &
Hepatology, outside the submitted work.
SCN reports grants from Ferring and personal fees

from Takeda, AbbVie, Janssen, and Tillotts, outside
the submitted work.
Joyce W Y Mak, Francis K L Chan,
*Siew C Ng
siewchienng@cuhk.edu.hk
Center for Gut Microbiota Research, Department of
Medicine and Therapeutics, Institute of Digestive
Disease, The Chinese University of Hong Kong,
Hong Kong Special Administrative Region, China
1 National Health Committee of the People’s
Republic of China, National Administration of
Traditional Chinese Medicine. Diagnostic and
therapeutic guidance for 2019 novel
coronavirus disease (version 5). http://www.
nhc.gov.cn/yzygj/s7653p/202002/
d4b895337e19445f8d728fcaf1e3e13a/files/
ab6bec7f93e64e7f998d802991203cd6.pdf
(accessed April 15, 2020).
2 Wong SH, Lui RNS, Sung JJY. COVID-19 and the
digestive system. J Gastroenterol Hepatol 2020;
published online March 25. DOI:10.1111/
jgh.15047.
3 Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics
of coronavirus disease 2019 in China.
N Engl J Med 2020; published online Feb 28.
DOI:10.1056/NEJMoa2002032.
4 Chen N, Zhou M, Dong X, et al.
Epidemiological and clinical characteristics of
99 cases of 2019 novel coronavirus
pneumonia in Wuhan, China: a descriptive
study. Lancet 395: 507–13.
5 Hempel S, Newberry SJ, Maher AR, et al.
Probiotics for the prevention and treatment of
antibiotic-associated diarrhea: a systematic
review and meta-analysis. JAMA 2012;
307: 1959–69.
6 Allen SJ, Wareham K, Wang D, et al.
Lactobacilli and Bifidobacteria in the prevention
of antibiotic-associated diarrhoea and
Clostridium difficile diarrhoea in older inpatients
(PLACIDE): a randomised, double-blind,
placebo-controlled, multicentre trial. Lancet
2013; 382: 1249–57.
7 King S, Glanville J, Sanders ME, Fitzgerald A,
Varley D. Effectiveness of probiotics on the
duration of illness in healthy children and
adults who develop common acute respiratory
infectious conditions: a systematic review and
meta-analysis. Br J Nutr 2014; 112: 41–54.
8 Hao Q, Dong BR, Wu T. Probiotics for
preventing acute upper respiratory tract
infections. Cochrane Database Syst Rev 2015;
CD006895.
9 Morrow LE, Kollef MH, Casale TB. Probiotic
prophylaxis of ventilator-associated pneumonia:
a blinded, randomized, controlled trial.
Am J Respir Crit Care Med 2010; 182: 1058–64.
10 Zeng J, Wang CT, Zhang FS, et al. Effect of
probiotics on the incidence of ventilator-
associated pneumonia in critically ill patients:
a randomized controlled multicenter trial.
Intensive Care Med 2016; 42: 1018–28.
11 Xu K, Cai H, Shen Y, et al. Management of corona
virus disease-19 (COVID-19): the Zhejiang
experience. Zhejiang Da Xue Xue Bao Yi Xue Ban
2020; 49: (in Chinese).
12 Feng Z, Wang Y, Qi W. The small intestine, an
underestimated site of SARS-CoV-2 infection:
from red queen effect to probiotics.
Preprints 2020; published online March 10.
DOI:10.20944/preprints202003.0161.v1
(preprint).
www.thelancet.com/gastrohep Vol 5 July 2020 645
Resumption of daily
services in a
gastroenterology
department in
Guangzhou, China, in
the wake of COVID-19
We read with interest the Rapid Review
by Iacucci and colleagues,1 which
examined how the coronavirus disease
2019 (COVID-19) pandemic was
affecting the use of endoscopy services
for inflammatory bowel disease,
management of emergency cases, and
prioritisation of access to endoscopy in
the post-pandemic period.
The peak of the initial COVID-19
outbreak appears to have passed in
China, with decreasing numbers of
new domestic cases observed since late
February.2 As a result of this decrease
in new cases, our gastroenterology
department at the First Affiliated
Hospital, Sun Yat-sen University,
Guangzhou, China, resumed daily
service on March 2, 2020. Before
admission, patients must make
appointments online and undergo
strict triage based on exposure history,
COVID-19 symptoms, and the medical
services they need.
Before they can receive further
medical services in our department,
patients who have fever or respiratory
symptoms, with or without a history
of exposure to COVID-19, must have
real-time PCR (rtPCR) testing of
severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) after
having throat swabs collected,
routine blood tests, and chest
CT at our hospital’s fever clinic.
Patients who have a clear exposure
history, oversea travel history, or
signs of inflammation on chest
CT images, and individuals in
need of hospitalisation, surgery,
chemotherapy, haemodialysis, or
other invasive procedures should
have throat swabs taken for
SARS-CoV-2 rtPCR testing, along
with routine blood tests and chest
Correspondence
CT if necessary. All other patients are
not being tested for SARS-CoV-2 by
rtPCR and are proceeding directly to
Published Online
different medical services on the basis May 4, 2020
https://doi.org/10.1016/
of their medical need. For example,
emergency patients are admitted or
S2468-1253(20)30133-3
For the Chinese translation see
referred to the emergency room and Online for appendix
patients who seek outpatient services
are referred to non-emergency clinics
for all types of digestive diseases or to
expert clinics for inflammatory bowel
disease, neuroendocrine tumours, etc.
Gastroenterologists and hepa­to­
lo­gists are responsible for this triage
in outpatient services. To prevent
patients from gathering (to ensure
adequate social distancing), clinic time
is allocated in 30-min blocks, with
patients making appointments by
smartphone app first. Only one patient
is allowed to enter the consulting
room at any time and is seen by one
physician in each consulting room.
Precautions against the airborne spread
of COVID-19, such as urging patients
to wear face masks and to keep 1 m
apart when waiting in line, are strictly
observed. For emergency patients
without SARS-CoV-2 rtPCR test results,
we observe meticulous protection
protocols to ensure lifesaving
operations are done and to prevent
potential nosocomial infection. For
example, medical workers operate in
an isolated ward with protective gear
including N95 masks, face shields
or goggles, disposable hat and shoe
covers, gowns, and double-layer rubber
gloves. We resumed non-emergency
clinics for all types of digestive disease,
seeing 50 patients per day in February,
increasing to 100–150 per day in March,
and reaching full capacity (300 cases
per day) from April 20, 2020. The
expert clinics resumed at half capacity
(an average of 60 cases per day) on
March 2, 2020, and have returned to
normal operation (120 cases per day)
since April 20, 2020.
For patients who need to be
admitted to hospital, only patients
and their next of kin who have
negative SARS-CoV-2 rtPCR results
from throat swabs are allowed to